Association analysis identifies 65 new breast cancer risk loci
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
- Teacher spread
- 0.284 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours. Genome-wide association studies for breast cancer have identified common genetic variation that influences susceptibility to this disease, but much of the genetic risk remains unexplained. Doug Easton and colleagues report a genome-wide association study for breast cancer in more than 122,000 cases and 105,000 controls. The authors genotyped a subset of these cases using OncoArray, a new, custom genome-wide single-nucleotide polymorphism (SNP) array for cancer genomics. Overall, they identify 65 loci newly associated with breast cancer susceptibility, and estimate that, together with 107 previously identified breast cancer susceptibility loci, these explain about 18 per cent of the familial relative risk of breast cancer. Polygenic risk scores may be used in risk prediction models and may improve early detection and targeted prevention of the disease. Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10−8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Nature
- Topic
- Genetic Associations and Epidemiology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- University of British ColumbiaUniversity Health NetworkPublic Health OntarioSimon Fraser UniversityMcGill UniversityLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalQueen's UniversityCentre Hospitalier de l’Université de MontréalUniversité LavalBC Cancer AgencyRoyal Victoria HospitalCentre hospitalier universitaire de QuébecMcGill University and Génome Québec Innovation CentreUniversity of Toronto
- Funders
- National Cancer InstituteNational Human Genome Research InstituteFogarty International CenterNational Institute of Mental HealthCanadian Institutes of Health ResearchMedical Research CouncilMinistero dello Sviluppo EconomicoWorld Health OrganizationEuropean CommissionNational Institutes of HealthCancer Research UKGovernment of CanadaFondation du cancer du sein du QuébecGenome CanadaFrancis Crick InstituteNational Institute of General Medical SciencesMinistère du Développement Économique, de l’Innovation et de l’ExportationNational Institute for Health and Care Research
- Keywords
- Breast cancerOncologyAssociation (psychology)MedicineGeneticsBiologyComputational biologyCancerPsychology
- Has abstract in OpenAlex
- yes